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Notice of Special Interest (NOSI): Integrative Omics Analysis of NHLBI TOPMed Data (Parent R01 Clinical Trial Not Allowed)

National Institutes of Health

The symptom-based diagnosis and treatment of heart, lung, blood, and sleep (HLBS) diseases has vastly improved in recent years, yet an understanding of the molecular mechanisms underlying many of these diseases has remained elusive. Furthermore, in most cases the impact of genetic variation on severity of disease and treatment outcomes remains unknown. Therefore, the NHLBI has created the Trans-omics for Precision Medicine (TOPMed) program, which aims to utilize genomics data to characterize a variety of HLBS diseases. TOPMed is well on its way to collecting whole genome sequence (WGS) from over 194,270 well-phenotyped individuals and is currently generating multi-omics data (e.g., over 31,852 RNA sequences, over 44,342 DNA methylation profiles, and 26,124 metabolomics profiles) from many of these individuals to complement whole genome sequence information.

Having produced an unprecedented volume of high-throughput data, TOPMed now seeks to turn its attention to effectively leveraging this resource to uncover biological function and disease pathobiology through novel systems biology analyses and the power of artificial intelligence (AI) and Machine Learning (ML). Although lower costs and technological improvements in sequencing technology have vastly expanded our ability to generate large volumes of omics data, the ability to analyze such large datasets to extract biologically meaningful insights remains challenging. Systems level models incorporating trans-omics analyses will be an important step in uncovering the underlying biological networks and the gene-gene and gene-environment interactions influencing disease and treatment outcomes. Thus, advanced analyses that incorporate genotype and phenotype datasets from thousands to tens of thousands of individuals are essential to move TOPMed to the next phase of discovery.

This notice applies to due dates on or after June 5, 2023 and subsequent receipt dates through May 7, 2026.

NOT-HL-23-067